北里大学薬学部微生物学教室

1. Salmonella pathogenesis and host defense mechanism

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative bacillus and causes gastroenteritis and systemic infections such as bacteremia. Two type III secretion systems (T3SS)-1 and T3SS-2 play crucial roles in Salmonella pathogenesis. We are interested in the effector proteins which hijack the host immune systems to promote bacterial dissemination to the systemic sites.

2. Molecular characterization of type III effectors in pathogenic Chromobacterium

Chromobacterium violaceum is an abundant component of the soil and water microbiota in tropical and subtropical regions around the world. Its high virulence in human infections and a mouse infection model involves the possession of several predicted virulence traits, including two distinct Cpi-1 and Cpi-2 T3SSs. In order to understand the molecular mechanisms regarding C. violaceum pathogenesis, we focus on the role of type III effectors exported by the C. violaceum Cpi-1 T3SS into host cells.

3. Molecular mechanisms of gut infection by enteropathogenic bacteria including Salmonella and Citrobacter rodentium

Enteropathogenic bacteria are prominent causes of foodborne diarrhea, worldwide. Unfortunately, vaccines are missing for most enteropathogenic bacteria. Furthermore, as antibiotic therapies are ineffective, alternative approaches for prevention or therapy will be definitely needed. Understanding the molecular mechanisms of gut infection by enteropathogenic bacteria leads to development of new therapeutic interventions for the infectious disease. We thus study the molecular pathogenesis of common enteropathogenic bacteria including Salmonella and Citrobacter rodentium.

4. Role of the intestinal epithelium-derived bactericidal lectin in bacterial gut infection

The mammalian intestinal epithelial tissues continuously encounter microbes including bacteria, fungi, viruses and parasites that could be enteropathogens. Thus, gut mucosal defense is critical for intestinal homeostasis and prevention of the infection by enteropathogens. Epithelial antimicrobial proteins have essential role in the mucosal defense by coping with the microbial challenges. The RegIII (regenerating gene family protein III) lectins belong to the antimicrobial proteins, and are expressed in epithelial cells of stomach, small intestine and colon. Importantly, expression of RegIII lectins is dramatically increased in response to bacterial gut colonization and pathogen infection leading to inflammation. Thus, aim of this study is deciphering the role of bactericidal RegIII lectins on bacterial gut infection.

5. Molecular mechanisms of gut colonization by Crohn’s disease-associated adherent-invasive Escherichia coli (AlEC)

Crohn’s disease (CD) is an inflammatory bowel disease that is caused by an aberrant mucosal immune response to microbial and environmental cues. Adherent-invasive E. coli (AIEC) pathotype has been implicated in the pathogenesis, yet the pathogenic mechanisms facilitating AIEC gut colonization are unknown. We thus uncover the underlying mechanism of AIEC gut colonization, and expect that our findings will lead to the development of therapeutic interventions for CD.

6. Genetic basis and molecular pathogenesis of enterohemorrhagic Escherichia coli (EHEC)

Ingestion of only 10–100 cells is enough to establish EHEC infection, which provoke diarrhea and hemorrhagic colitis, and hemolytic uremic syndrome. The strategies that allow for rapid adaptation of EHEC to various stresses in the gastrointestinal tract, and that enable EHEC to colonize a suitable niche are essential for the establishment of EHEC infection. These strategies involve various mechanisms that regulate gene expression, one of which is post-transcriptionally regulation by small regulatory RNAs (sRNAs). We are trying to clarify the sRNAs-mediated regulatory networks underpinning the pathogenicity of EHEC.

7. Vaginal Lactobacillus species-specific impacts on the human female reproductive tract epithelial barrier properties

The human vaginal microbiota in reproductive age is mainly dominated by one of four Lactobacillus species: L. crispatus, L. gasseri, L. iners, and L. jensenii. Their presence, especially L. crispatus, is well correlated with low bacterial diversity and overall female reproductive tract health. However, L. iners is unique in that it has been associated with the acquisition of sexually transmitted infections, preterm labor, any prevalent HPV, and cervical dysplasia/cancer compared with L. crispatus. To maintain female reproductive tract health, clarification of the mechanisms of vaginal Lactobacillus-species specific impacts to female reproductive tract homeostasis is needed. To investigate the mechanisms, we have been trying to clarify the interaction between vaginal lactobacilli and female reproductive tract epithelial barrier properties using a three-dimensional (3-D) rotating wall vessels (RWV) bioreactor system that recapitulates many physiologically relevant barrier properties.